The present invention relates to ophthalmic compositions that relieve eye irritation or dryness and provide lubrication for the eyes. More particularly, the invention relates to ophthalmic solutions that function as artificial tears and can be used, as needed, for temporary relief of and protection against eye irritation.
Many people suffer from temporary or chronic eye conditions wherein the eye's tear system fails to provide adequate tear volume or tear film stability to remove irritating environmental contaminants such as dust, pollen or the like. Where the tear film on ocular surfaces becomes discontinuous, the condition is often called "dry eye".
Such failures of the tear system result in significant personal discomfort, such as dry, itching, burning and irritating eyes. Treatment typically involves applying a slightly viscous solution in drop form to the eyes to provide at least a temporary wetting before the solution evaporates or is wiped away by operation of the eyelids. Since the solution tends to be cleared from the eye rather quickly, frequent dosing is generally necessary.
A key element of an artificial tears solution is a polymer system designed to mimic the action of mucin and or/lipids, which are the principal active natural components of tear fluid. The polymer system selected for artificial tears acts as a wetting agent in the eye and is responsible for contributing to tear film stability.
In addition to the active polymer system ingredients, a preservative system that is effective for maintaining solution sterility is typically necessary. Its purpose is to prevent bacteria and other organisms from contaminating the solution after its container has been opened and an initial dose has been used. Such a preservative is a necessary component of artificial tears where packaging is in other than single dose units.
An example of a prior artificial tears solution is described by Bapatla et al in U.S. Pat. No. 4,120,949. Bapatla pointed out that earlier commercially available artificial tear solutions had been either excessively viscous and, therefore, difficult to use or were so low in viscosity that the solution could not form a sufficiently long lasting film. Bapatla's artificial tear composition said to have a relatively long film life, contains polyvinyl alcohol (0.1-10.0%), hydroxyethyl cellulose (0.1-5.0%) and polyvinylpyrrolidone (0.1-20.0%). Bapatala's Examples report viscosities ranging between 5 and 270 cps. However, all but one are relatively high viscosities, in the 80-270 cps range. Surface tension of the solutions of the Examples ranged from between 33 and 45 dynes/cm.
In a review article on surface interfacial and molecular aspects of polymer bioadhesion of soft tissues, Nikolaos A. Pappas and Pierre A. Buri [Journal of Controlled Release, 2(1985) 257-275] quote A. J. Kinlock [J. Mater. Sci. 15 (1980) (2141] as stating that bioadhesion is enhanced for liquid adhesive materials characterized by zero or near zero contact angles and having relatively low viscosities. Tiffany et al, in "Tear Film Stability and Tear Surface Tension" Current Eye Research, Vol. 8, No. 5 (1989), finds a negative correlation between surface tension and break-up-time for tear film on the human eye. These works suggest that low surface tension may be a useful factor for artificial tears that must adhere readily to corneal surfaces.
A particularly useful wetting agent that does not unduly increase the viscosity of ophthalmic solutions is polyvinylpyrrolidone (PVP). PVP has a number of other characteristics that makes it useful in combination with the various well known components in ophthalmic solutions.
Rankin, in U.S. Pat. No. 3,920,810, notes that polyvinylpyrrolidone acts as a detoxicant, binding anti-toxins present in eye fluids and rendering them harmless. PVP also acts to protect a treatment solution by preventing its breakdown, through particle agglomeration. Additionally, PVP acts as a demulcent lubricant by means of a combination of adhesive and lubricating properties that aid in the spreading of the viscous solution.
Preferred preservatives utilized in ophthalmic solutions may include quaternary ammonium compounds, particularly benzalkonium chloride (BAK), as described by Hecht et al in U.S. Pat. No. 4,039,662. Although BAK is an effective preferred preservative, it is often limited in concentration and, hence, usefulness because of some users' sensitivity thereto.
Blanco et al, in U.S. Pat. No. 4,029,817, teaches that quaternary ammonium compounds, e.g. benzalkonium chloride, when combined with a detoxifying amount of certain polymers, may be utilized in contact lens cleaning solutions at BAK concentration levels otherwise known to be irritating and potentially harmful. A list of suitable polymers includes, among others, polyvinylpyrrolidone.
It would be desirable to provide a formulation that provides effective relief from dry and irritating eye conditions by means of components that combine to provide good wetting and retainability in the eye which formulation also includes a reliable preservative that is rendered substantially less irritating or non-irritating.